DOCSLIB.ORG

TRPS and Migraine Romina Nassini*, Francesco De Cesaris, Pamela Pedretti and Pierangelo Geppetti

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
TRPS and Migraine Romina Nassini*, Francesco De Cesaris, Pamela Pedretti and Pierangelo Geppetti The Open Drug Discovery Journal, 2010, 2, 55-63 55 Open Access TRPS and Migraine Romina Nassini*, Francesco De Cesaris, Pamela Pedretti and Pierangelo Geppetti Headache Center, University Hospital Careggi and Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy Abstract: Migraine is a highly prevalent, disabling neurovascular disorder characterized by a combination of headache, nausea and altered sensory processing such as photophobia. Migraine has a strong genetic background but the molecular pathways that result in a migraine attack, and the role of various triggers, are poorly understood. The throbbing and pulsating pain associated with the headache phase of migraine attack implies an important role for the nociceptive activation of trigeminal intracranial afferents that contain calcitonin gene-related peptide (CGRP). Neurogenic inflammation triggered by the release of CGRP is now recognized as a significant underlying event in migraine. Indeed, CGRP receptor antagonists, the so-called “gepants”, have already proved effective in clinical trials as novel, migraine- specific drugs. An alternative therapeutic approach is the modulation of CGRP release. As potential targets, the transient receptor potential (TRP) channels expressed by a subpopulation of CGRP-containing nociceptive primary sensory neurons are gaining increasing prominence, principally because of the recent discovery of a variety of endogenous and exogenous TRP agonists known to induce migraine attack as well as their emerging role in neuropeptide release. The present review focuses on the potential role of the different TRP channels, especially TRPV1, in the migraine mechanism. Keywords: TRP channel, TRPV1, migraine, capsaicin, CGRP, neurogenic inflammation, clinical trials, heat, neuropeptides, geptins. INTRODUCTION the disorder. There is growing evidence that the initiating event (though influenced by several contributing factors such Migraine is a common, disabling and economically as stress, environmental agents or hormones) occurs in the costly [1, 2] neurovascular disorder that affects a significant central nervous system (CNS) and somehow involves portion of the population, an estimated 13 million trigeminal neurons [4, 7]. Americans. Underlying migraine are neurovascular events that result in the dilatation of blood vessels and subsequent In recent years, the hypothesis that the release of nerve activation and pain [3]. Disability due to migraine is calcitonin gene-related peptide (CGRP) from sensory severe. Although migraine involves patients from infancy neurons stimulates sensory nerve transmission and dilates through senescence, it is especially prevalent among women cranial blood vessels has gained experimental support [8], between the ages of 35 and 45 years, with one in five suggesting a major role of CGRP in the pathogenesis of individuals reporting one or more migraine headaches per migraine. In this perspective, CGRP receptor antagonists year in this age group. Migraine care is complicated by the have become attractive as potential migraine-specific drugs. fact that underlying triggers and pathways are poorly Moreover, it has been demonstrated that other brain regions understood. Genetic abnormalities may initiate the alteration with enriched CGRP receptor expression, such as the of the response threshold to migraine-specific triggers in the hypothalamus, are activated during spontaneous migraine brain, but the specific gene(s) involved have not yet been attacks [9]. The first experimental observations that CGRP determined [4]. The migraine attack can be precipitated by (8–37), a truncated form of CGRP [10], behaved as a an extraordinary variety of stimuli, including psychological competitive and selective antagonist of the biological effects stress factors, excessive ingestion of alcoholic beverages, of CGRP, including smooth muscle relaxation, were not menstrual cycle, and changes in barometric pressure, anti- pursued, mainly because of the short biological half-life of angina medicines, sleep deprivation, and other factors [5, 6]. this peptide. More recently, the inhibition of CGRP receptors The lack of knowledge about the pathways underlying with two chemically unrelated CGRP receptor antagonists, migraine attack is one of the major obstacles to the discovery telcagepant and olcegepant (collectively referred to as of better and safer drugs. Uncertainty also exists regarding “gepants”) [11, 12], has been successfully used to treat acute the precise site of action and molecular targets of the various migraine [13-15]. drugs used for both prophylaxis and symptomatic relief of CGRP is contained in neurons of the central and migraine attack. However, in recent years much progress has peripheral nervous system. In the periphery, except for been made to better understand the underlying mechanism of intrinsic neurons of the gastrointestinal tract, CGRP is strictly confined to a subpopulation of somatosensory neurons with cell bodies located in the dorsal root (DRG), *Address correspondence to this author at the Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 vagal (VG) and trigeminal (TG) ganglia. The release of Florence, Italy; Tel: +39 055 427 1417; Fax: +39 055 427 1280; sensory neuropeptides, including CGRP, undergoes fine E-mail: [email protected] tuning by a series of mediators and agents that act at 1877-3818/10 2010 Bentham Open 56 The Open Drug Discovery Journal, 2010, Volume 2 Nassini et al. prejunctional receptors/channels on sensory nerve terminals. symptoms of migraine attack. A considerable number of A wide array of G protein-coupled receptors are involved in animal and human studies have been carried out to better this process, including those for bradykinin, prostanoids, understand the physiology and pharmacology of the sensory opioids, 5-hydroxytryptamine (5-HT1 receptor), histamine innervation of the dura mater and cranial vessels. Evidence (H3 receptor), neuropeptide Y, somatostatin, vasoactive obtained in experimental animals suggests that the migraine intestinal polypeptide (VIP), purines and galanin. One of the aura is the clinical manifestation of a cortical spreading major mechanisms that promotes CGRP release from depression (CSD) [24, 25]. It has been proposed that the sensory neurons is the activation of members of the transient neural changes caused by the slow depolarizing wave of receptor potential (TRP) family of channels, in particular CSD eventually result in the painful symptoms associated TRPV1 (Founding member of the Transient Receptor with vasodilatation of the cranial blood vessels and other Potential Vanilloid family). The present review focuses on phenomena of the migraine attack [4]. However, while the distribution and activation mechanisms of the different tonabersat, a drug specifically developed to block CSD, did TRP channels expressed by subsets of trigeminal primary abolish the aura, it failed to prevent the headache of migraine sensory neurons, and discusses the potential of this receptor attack, in either an acute or a chronic setting [26-28]. This family in migraine mechanisms. finding indicates that CSD and the resulting aura are epiphenomena, but not the cause of the pain of migraine PRIMARY SENSORY NEURONS AND NEUROGENIC attack. INFLAMMATION: ROLE IN MIGRAINE In experimental animals, particularly rodents, stimulation More than 70 years ago, Sir Thomas Lewis, in his of a subset of peptidergic somatosensory neurons leads to the pioneering studies [16], precisely defined the dual release of various neuropeptides, specifically CGRP and the 'nocifensor' role of a subset of primary sensory neurons. One tachykinins SP and neurokinin A (NKA). Activation of segment of the widely branching sensory fiber network of CGRP receptors and tachykinin (NK1, NK2 and NK3) this neuron responds to the injury and generates action receptors located on effector cells at the peripheral level potentials which are carried antidromically to collateral causes a series of inflammatory responses, collectively branches, where these branches release a chemical substance referred to as ‘neurogenic inflammation’ [17]. This term that causes a flare response and increases the sensitivity of refers to a cascade of events that occur mainly, but not other sensory fibers responsible for pain. It has been exclusively, at the perivascular level. Indeed, CGRP-, SP-, proposed that the neurons which mediate these responses and NKA-release induce vasodilatation in arterial vessels, belong to a previously unrecognized subgroup, and termed and plasma protein extravasation and leukocyte adhesion to ‘nocifensors’ because of their dual function. The first the vascular endothelium of postcapillary venules [17]. function of these nocifensors is to sense nociceptive/pain These two latter responses are mediated by NK1 receptor stimuli. The second is to promote a first line of defense, activation on endothelial cells, which results in a calcium- mediated through neurovascular responses, which includes dependent activation of intracellular contractile elements, arterial vasodilatation, plasma protein extravasation, and leading to the opening of gaps between cells and the other responses. All these responses are associated with the development of inflammatory edema. In the dura mater, capacity to release neuropeptides from peripheral terminals neurogenic plasma extravasation mediated by NK1 receptors of primary sensory neurons.
Load more

Recommended publications
  • Pepperspray, CS, & Other 'Less-Lethal' Weapons
    CONTENTS: Protective Measures: p.26-27 Pepperspray: p.2-9, 14-15 Chemical Data Table: p.30 CS/CN: p.10-16 Risk Groups: p.14-15 When to do what / Other Gas Types: p. 12 Asthma: p.14 treatment algorithm: p.4 Rubber Bullets: p.19-21 Nightsticks/Batons: p.17 LAW: p.6 Concussion Grenades: p.22 CR: p.12 VOFIBA: p.7 Fear: p.24 CA: p.12 Making Remedies: p.13 Tasers: p.18 DM: p.12 Sample Card for Handing Out: Shamelessly adapted from the Black Cross Radical Health Collective, www.blackcrosscollective.org If your condition is worsening, go to an emergency room. Basic preparations: Stick with your buddy. Pepperspray, CS, & Other Work with an affinity group. Bring water. Vulnerable people like asthmatics may want to “Less-Lethal” Weapons (your logo here) avoid chemical weapons. You must remove small children from the area BEFORE Used by Rioting Police to Suppress Dissent chemical weapons are used. Check out our w h e n P o l i t r i c k s & Te l e v i s i o n f a i l t o d o s o . website <www.---.org> for lots more info on how to prepare. v3.3 Useful Numbers: Serious injuries: If you don’t know how to treat Medical Emergency: 911 an injury, get a medic, or call 911. Don’t treat Copwatch: 123-4560 someone if you don’t know how. If you are Convergence Ctr Aid Station:123-4567 injured by the police, get to a nurse practitioner, Aftercare Clinic: 123-4568 physician’s assistant, or doctor immediately Legal Team: 123-4565 and have your injury documented in case you Public Defenders: 123-4569 decide to sue.
    [Show full text]
  • Extensive Exposure to Tear Gases in Ankara
    Turk Thorac J 2019 DOI: 10.5152/TurkThoracJ.2018.18096 Original Article Extensive Exposure to Tear Gases in Ankara Aslıhan Ilgaz1 , Filiz Çağla Küçük Uyanusta2 , Peri Arbak3 , Arif Müezzinoğlu4 , Tansu Ulukavak Çiftçi5 , Serdar Akpınar6 , Hikmet Fırat6 , Selma Fırat Güven7 , Bülent Çiftçi8 , Selen Karaoğlanoğlu9 , Elif Dağlı10 , Feyza Erkan11 1Clinic of Pulmonary Diseases, Middle East Technical University, Medical Center, Ankara, Turkey 2Clinic of Pulmonary Diseases, ARTE Hekimköy Medical Center, Ankara, Turkey 3Department of Chest Diseases, Düzce University School of Medicine, Düzce, Turkey 4Ankara Chamber of Medical Doctors, Commission of Workers’ Health and Occupational Physicians, Ankara, Turkey 5Department of Pulmonary Diseases, Gazi University School of Medicine, Ankara, Turkey 6Clinic of Chest Diseases, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey 7Sleep Disorders Center, Atatürk Chest Diseases, Thoracic Surgery Training and Research Hospital, Ankara, Turkey 8Department of Pulmonary Diseases, Bozok University School of Medicine, Yozgat, Turkey 9Department of Pulmonary Diseases, Ordu University School of Medicine, Ordu, Turkey 10Clinic of Child Chest Diseases, Acıbadem Fulya Hospital, İstanbul, Turkey 11Department of Pulmonary Medicine, İstanbul University İstanbul School of Medicine, İstanbul, Turkey Cite this article as: Ilgaz A, Küçük Uyanusta FÇ, Arbak P, et al. Extensive Exposure to Tear Gases in Ankara. Turk Thorac J 2019; DOI: 10.5152/TurkThoracJ.2018.18096 Abstract OBJECTIVES: The most common chemical substances used as mass control agents are chloroacetophenone, chlorobenzylidene malono- nitrile, and oleoresin capsicum. These agents not only have local and rapid effects but also have systemic and long-term effects. The aim of the present study was to discuss the patterns of tear gas exposure and to investigate its effects on respiratory functions.
    [Show full text]
  • Amplification of Oxidative Stress by a Dual Stimuli-Responsive Hybrid Drug
    ARTICLE Received 11 Jul 2014 | Accepted 12 Mar 2015 | Published 20 Apr 2015 DOI: 10.1038/ncomms7907 Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death Joungyoun Noh1, Byeongsu Kwon2, Eunji Han2, Minhyung Park2, Wonseok Yang2, Wooram Cho2, Wooyoung Yoo2, Gilson Khang1,2 & Dongwon Lee1,2 Cancer cells, compared with normal cells, are under oxidative stress associated with the increased generation of reactive oxygen species (ROS) including H2O2 and are also susceptible to further ROS insults. Cancer cells adapt to oxidative stress by upregulating antioxidant systems such as glutathione to counteract the damaging effects of ROS. Therefore, the elevation of oxidative stress preferentially in cancer cells by depleting glutathione or generating ROS is a logical therapeutic strategy for the development of anticancer drugs. Here we report a dual stimuli-responsive hybrid anticancer drug QCA, which can be activated by H2O2 and acidic pH to release glutathione-scavenging quinone methide and ROS-generating cinnamaldehyde, respectively, in cancer cells. Quinone methide and cinnamaldehyde act in a synergistic manner to amplify oxidative stress, leading to preferential killing of cancer cells in vitro and in vivo. We therefore anticipate that QCA has promising potential as an anticancer therapeutic agent. 1 Department of Polymer Á Nano Science and Technology, Polymer Fusion Research Center, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea. 2 Department of BIN Convergence Technology, Chonbuk National University, Backje-daero 567, Jeonju 561-756, Korea. Correspondence and requests for materials should be addressed to D.L. (email: [email protected]). NATURE COMMUNICATIONS | 6:6907 | DOI: 10.1038/ncomms7907 | www.nature.com/naturecommunications 1 & 2015 Macmillan Publishers Limited.
    [Show full text]
  • TRPM8 Activation by Menthol, Icilin, and Cold Is Differenially Modulated by Intracellular Ph
    5364 • The Journal of Neuroscience, June 9, 2004 • 24(23):5364–5369 Cellular/Molecular TRPM8 Activation by Menthol, Icilin, and Cold Is Differentially Modulated by Intracellular pH David A. Andersson, Henry W. N. Chase, and Stuart Bevan Novartis Institute for Medical Sciences, London WC1E 6BN, United Kingdom TRPM8 is a nonselective cation channel activated by cold and the cooling compounds menthol and icilin (Peier et al., 2002). Here, we have used electrophysiology and the calcium-sensitive dye Fura-2 to study the effect of pH and interactions between temperature, pH, and the two chemical agonists menthol and icilin on TRPM8 expressed in Chinese hamster ovary cells. Menthol, icilin, and cold all evoked 2ϩ ϩ stimulus-dependent [Ca ]i responses in standard physiological solutions of pH 7.3. Increasing the extracellular [H ] from pH 7.3 to approximately pH 6 abolished responses to icilin and cold stimulation but did not affect responses to menthol. Icilin concentration– response curves were significantly shifted to the right when pH was lowered from 7.3 to 6.9, whereas those with menthol were unaltered in solutions of pH 6.1. When cells were exposed to solutions in the range of pH 8.1–6.5, the temperature threshold for activation was elevatedathigherpHanddepressedatlowerpH.Superfusingcellswithalowsubactivatingconcentrationoficilinormentholelevatedthe 2ϩ threshold for cold activation at pH 7.4, but cooling failed to evoke [Ca ]i responses at pH 6 in the presence of either agonist. In voltage-clamp experiments in which the intracellular pH was buffered to different levels, acidification reduced the current amplitude of icilin responses and shifted the threshold for cold activation to lower values with half-maximal inhibition at pH 7.2 and pH 7.6.
    [Show full text]
  • Current Awareness in Clinical Toxicology Editors: Damian Ballam Msc and Allister Vale MD
    Current Awareness in Clinical Toxicology Editors: Damian Ballam MSc and Allister Vale MD April 2015 CONTENTS General Toxicology 9 Metals 44 Management 22 Pesticides 49 Drugs 23 Chemical Warfare 51 Chemical Incidents & 36 Plants 52 Pollution Chemicals 37 Animals 52 CURRENT AWARENESS PAPERS OF THE MONTH Acute toxicity profile of tolperisone in overdose: observational poison centre-based study Martos V, Hofer KE, Rauber-Lüthy C, Schenk-Jaeger KM, Kupferschmidt H, Ceschi A. Clin Toxicol 2015; online early: doi: 10.3109/15563650.2015.1022896: Introduction Tolperisone is a centrally acting muscle relaxant that acts by blocking voltage-gated sodium and calcium channels. There is a lack of information on the clinical features of tolperisone poisoning in the literature. The aim of this study was to investigate the demographics, circumstances and clinical features of acute overdoses with tolperisone. Methods An observational study of acute overdoses of tolperisone, either alone or in combination with one non-steroidal anti-inflammatory drug in a dose range not expected to cause central nervous system effects, in adults and children (< 16 years), reported to our poison centre between 1995 and 2013. Current Awareness in Clinical Toxicology is produced monthly for the American Academy of Clinical Toxicology by the Birmingham Unit of the UK National Poisons Information Service, with contributions from the Cardiff, Edinburgh, and Newcastle Units. The NPIS is commissioned by Public Health England Results 75 cases were included: 51 females (68%) and 24 males (32%); 45 adults (60%) and 30 children (40%). Six adults (13%) and 17 children (57%) remained asymptomatic, and mild symptoms were seen in 25 adults (56%) and 10 children (33%).
    [Show full text]
  • Chronic Pelvic Pain M
    Guidelines on Chronic Pelvic Pain M. Fall (chair), A.P. Baranowski, S. Elneil, D. Engeler, J. Hughes, E.J. Messelink, F. Oberpenning, A.C. de C. Williams © European Association of Urology 2008 TABLE OF CONTENTS PAGE 1. INTRODUCTION 5 1.1 The guideline 5 1.1.1 Publication history 5 1.2 Level of evidence and grade recommendations 5 1.3 References 6 1.4 Definition of pain (World Health Organization [WHO]) 6 1.4.1 Innervation of the urogenital system 7 1.4.2 References 8 1.5 Pain evaluation and measurement 8 1.5.1 Pain evaluation 8 1.5.2 Pain measurement 8 1.5.3 References 9 2. CHRONIC PELVIC PAIN 9 2.1 Background 9 2.1.1 Introduction to urogenital pain syndromes 9 2.2 Definitions of chronic pelvic pain and terminology (Table 4) 11 2.3 Classification of chronic pelvic pain syndromes 12 Table 3: EAU classification of chronic urogenital pain syndromes (page 10) Table 4: Definitions of chronic pain terminology (page 11) Table 5: ESSIC classification of types of bladder pain syndrome according to the results of cystoscopy with hydrodistension and of biopsies (page 13) 2.4 References 13 2.5 An algorithm for chronic pelvic pain diagnosis and treatment 13 2.5.1 How to use the algorithm 13 2.6 Prostate pain syndrome (PPS) 15 2.6.1 Introduction 16 2.6.2 Definition 16 2.6.3 Pathogenesis 16 2.6.4 Diagnosis 17 2.6.5 Treatment 17 2.6.5.1 Alpha-blockers 17 2.6.5.2 Antibiotic therapy 17 2.6.5.3 Non-steroidal anti-inflammatory drugs (NSAIDs) 17 2.6.5.4 Corticosteroids 17 2.6.5.5 Opioids 17 2.6.5.6 5-alpha-reductase inhibitors 18 2.6.5.7 Allopurinol 18 2.6.5.8
    [Show full text]
  • G Protein-Coupled Receptors As Therapeutic Targets for Multiple Sclerosis
    npg GPCRs as therapeutic targets for MS Cell Research (2012) 22:1108-1128. 1108 © 2012 IBCB, SIBS, CAS All rights reserved 1001-0602/12 $ 32.00 npg REVIEW www.nature.com/cr G protein-coupled receptors as therapeutic targets for multiple sclerosis Changsheng Du1, Xin Xie1, 2 1Laboratory of Receptor-Based BioMedicine, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sci- ences and Technology, Tongji University, Shanghai 200092, China; 2State Key Laboratory of Drug Research, the National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shou Jing Road, Pudong New District, Shanghai 201203, China G protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmit- ters and environmental stimulants. They are considered as the most successful therapeutic targets for a broad spec- trum of diseases. Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated de- myelination and degeneration of the central nervous system (CNS). It is the leading cause of non-traumatic disability in young adults. Great progress has been made over the past few decades in understanding the pathogenesis of MS. Numerous data from animal and clinical studies indicate that many GPCRs are critically involved in various aspects of MS pathogenesis, including antigen presentation, cytokine production, T-cell differentiation, T-cell proliferation, T-cell invasion, etc. In this review, we summarize the recent findings regarding the expression or functional changes of GPCRs in MS patients or animal models, and the influences of GPCRs on disease severity upon genetic or phar- macological manipulations.
    [Show full text]
  • Screening of Bacterial Quorum Sensing Inhibitors in a Vibrio fischeri Luxr-Based Synthetic Fluorescent E
    pharmaceuticals Article Screening of Bacterial Quorum Sensing Inhibitors in a Vibrio fischeri LuxR-Based Synthetic Fluorescent E. coli Biosensor Xiaofei Qin 1,2, Celina Vila-Sanjurjo 2,3, Ratna Singh 4, Bodo Philipp 5 and Francisco M. Goycoolea 2,6,* 1 Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, China; [email protected] 2 Laboratory of Nanobiotechnology, Institute of Plant Biology and Biotechnology, University of Münster, Schlossplatz 8, D-48143 Münster, Germany; [email protected] 3 Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Campus Vida, s/n, 15782 Santiago de Compostela, Spain 4 Laboratory of Molecular Phytopathology and Renewable Resources, Institute of Plant Biology and Biotechnology, University of Münster, Schlossplatz 8, D-48143 Münster, Germany; [email protected] 5 Institute of Molecular Microbiology and Biotechnology, University of Münster, Corrensstraße 3, D-48149 Münster, Germany; [email protected] 6 School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK * Correspondence: [email protected]; Tel.: +44-1133-431412 Received: 13 August 2020; Accepted: 18 September 2020; Published: 22 September 2020 Abstract: A library of 23 pure compounds of varying structural and chemical characteristics was screened for their quorum sensing (QS) inhibition activity using a synthetic fluorescent Escherichia coli biosensor that incorporates a modified version of lux regulon of Vibrio fischeri. Four such compounds exhibited QS inhibition activity without compromising bacterial growth, namely, phenazine carboxylic acid (PCA), 2-heptyl-3-hydroxy-4-quinolone (PQS), 1H-2-methyl-4-quinolone (MOQ) and genipin. When applied at 50 µM, these compounds reduced the QS response of the biosensor to 33.7% 2.6%, ± 43.1% 2.7%, 62.2% 6.3% and 43.3% 1.2%, respectively.
    [Show full text]
  • Cinnamaldehyde Induces Release of Cholecystokinin and Glucagon-Like
    animals Article Cinnamaldehyde Induces Release of Cholecystokinin and Glucagon-Like Peptide 1 by Interacting with Transient Receptor Potential Ankyrin 1 in a Porcine Ex-Vivo Intestinal Segment Model Elout Van Liefferinge 1,* , Maximiliano Müller 2, Noémie Van Noten 1 , Jeroen Degroote 1 , Shahram Niknafs 2, Eugeni Roura 2 and Joris Michiels 1 1 Laboratory for Animal Nutrition and Animal Product Quality (LANUPRO), Department of Animal Sciences and Aquatic Ecology, Ghent University, 9000 Ghent, Belgium; [email protected] (N.V.N.); [email protected] (J.D.); [email protected] (J.M.) 2 Centre for Nutrition and Food Sciences, Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St. Lucia, QLD 4072, Australia; [email protected] (M.M.); [email protected] (S.N.); [email protected] (E.R.) * Correspondence: [email protected] Simple Summary: The gut is able to “sense” nutrients and release gut hormones to regulate diges- tive processes. Accordingly, various gastrointestinal cell types possess transient receptor potential channels, cation channels involved in somatosensation, thermoregulation and the sensing of pungent and spicy substances. Recent research shows that both channels are expressed in enteroendocrine Citation: Van Liefferinge, E.; Müller, M.; Van Noten, N.; Degroote, J.; cell types responsible for the release of gut peptide hormones such as Cholecystokinin (CCK) and Niknafs, S.; Roura, E.; Michiels, J. Glucagon-like Peptide-1 (GLP-1). A large array of herbal compounds, used in pig nutrition mostly for Cinnamaldehyde Induces Release of their antibacterial and antioxidant properties, are able to activate these channels. Cinnamaldehyde, Cholecystokinin and Glucagon-Like occurring in the bark of cinnamon trees, acts as an agonist of Transient Receptor Potential Ankyrin 1 Peptide 1 by Interacting with (TRPA1)-channel.
    [Show full text]
  • Allicin Protects Against Lipopolysaccharide-Induced Acute Lung Injury by Up-Regulation of Claudin-4
    Zheng et al Tropical Journal of Pharmaceutical Research July 2014; 13 (7): 1063-1069 ISSN: 1596-5996 (print); 1596-9827 (electronic) © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved. Available online at http://www.tjpr.org http://dx.doi.org/10.4314/tjpr.v13i7.8 Original Research Article Allicin Protects against Lipopolysaccharide-Induced Acute Lung Injury by Up-Regulation of Claudin-4 Yue-liang Zheng, Wen-wei Cai, Guang-zhao Yan, Yuan-zhan Xu and Mei-qi Zhang* Department of Emergency, Zhejiang Provincial People's Hospital, Hangzhou 310014, China *For correspondence: Email: [email protected]; Tel: +86-0571-85893631 Received: 8 January 2014 Revised accepted: 31 May 2014 Abstract Purpose: To investigate the effect of allicin, an active component of garlic, on lipopolysaccharide (LPS)- induced acute lung injury. Methods: Wistar rats were subjected to LPS intravenous injection with or without allicin treatment to induce acute lung injury (ALI) model. Also, A549 cells were stimulated with LPS in the presence and absence of allicin. HE staining was used to detect pathological changes in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was performed to measure cytokine content. Cell viability was measured by CCK-8 and EdU incorporation assay. Genes expression was determined by real time polymerase chain reaction (PCR) and Western blot. Flow cytometry was applied to measure cell apoptosis. Results: In vivo data showed that pulmonary edema, inflammatory cytokines expression and pathological changes were significantly attenuated in LPS-induced ALI after treatment with allicin (p < 0.05) while in vitro results indicate that allicin administration significantly improved the A549 cell viability in a dose-dependent manner as measured by CCK-8 and EdU incorporation assay.
    [Show full text]
  • A Review of the Effects of Pain and Analgesia on Immune System Function and Inflammation: Relevance for Preclinical Studies
    Comparative Medicine Vol 69, No 6 Copyright 2019 December 2019 by the American Association for Laboratory Animal Science Pages 520–534 Overview A Review of the Effects of Pain and Analgesia on Immune System Function and Inflammation: Relevance for Preclinical Studies George J DeMarco1* and Elizabeth A Nunamaker2 One of the most significant challenges facing investigators, laboratory animal veterinarians, and IACUCs, is how to bal- ance appropriate analgesic use, animal welfare, and analgesic impact on experimental results. This is particularly true for in vivo studies on immune system function and inflammatory disease. Often times the effects of analgesic drugs on a particu- lar immune function or model are incomplete or don’t exist. Further complicating the picture is evidence of the very tight integration and bidirectional functionality between the immune system and branches of the nervous system involved in nociception and pain. These relationships have advanced the concept of understanding pain as a protective neuroimmune function and recognizing pathologic pain as a neuroimmune disease. This review strives to summarize extant literature on the effects of pain and analgesia on immune system function and inflammation in the context of preclinical in vivo studies. The authors hope this work will help to guide selection of analgesics for preclinical studies of inflammatory disease and immune system function. Abbreviations and acronyms: CB,Endocannabinoid receptor; CD,Crohn disease; CFA, Complete Freund adjuvant; CGRP,Calcitonin gene-related
    [Show full text]
  • Purinergic P2 Receptors As Targets for Novel Analgesics
    Pharmacology & Therapeutics 110 (2006) 433 – 454 www.elsevier.com/locate/pharmthera Purinergic P2 receptors as targets for novel analgesics Geoffrey Burnstock * Autonomic Neuroscience Centre, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK Abstract Following hints in the early literature about adenosine 5V-triphosphate (ATP) injections producing pain, an ion-channel nucleotide receptor was cloned in 1995, P2X3 subtype, which was shown to be localized predominantly on small nociceptive sensory nerves. Since then, there has been an increasing number of papers exploring the role of P2X3 homomultimer and P2X2/3 heteromultimer receptors on sensory nerves in a wide range of organs, including skin, tongue, tooth pulp, intestine, bladder, and ureter that mediate the initiation of pain. Purinergic mechanosensory transduction has been proposed for visceral pain, where ATP released from epithelial cells lining the bladder, ureter, and intestine during distension acts on P2X3 and P2X2/3, and possibly P2Y, receptors on subepithelial sensory nerve fibers to send messages to the pain centers in the brain as well as initiating local reflexes. P1, P2X, and P2Y receptors also appear to be involved in nociceptive neural pathways in the spinal cord. P2X4 receptors on spinal microglia have been implicated in allodynia. The involvement of purinergic signaling in long-term neuropathic pain and inflammation as well as acute pain is discussed as well as the development of P2 receptor antagonists as novel analgesics. D
    [Show full text]